Checkpoint blockade in cancer immunotherapy Journal Article
| Authors: | Korman, A. J.; Peggs, K. S.; Allison, J. P. |
| Article Title: | Checkpoint blockade in cancer immunotherapy |
| Abstract: | The progression of a productive immune response requires that a number of immunological checkpoints be passed. Passage may require the presence of excitatory costimulatory signals or the avoidance of negative or coinhibitory signals, which act to dampen or terminate immune activity. The immunoglobulin superfamily occupies a central importance in this coordination of immune responses, and the CD28/cytotoxic T-lymphocyte antigen-4 (CTLA-4):B7.1/B7.2 receptor/ligand grouping represents the archetypal example of these immune regulators. In part the role of these checkpoints is to guard against the possibility of unwanted and harmful self-directed activities. While this is a necessary function, aiding in the prevention of autoimmunity, it may act as a barrier to successful immunotherapies aimed at targeting malignant self-cells that largely display the same array of surface molecules as the cells from which they derive. Therapies aimed at overcoming these mechanisms of peripheral tolerance, in particular by blocking the inhibitory checkpoints, offer the potential to generate antitumor activity, either as monotherapies or in synergism with other therapies that directly or indirectly enhance presentation of tumor epitopes to the immune system. Such immunological molecular adjuvants are showing promise in early clinical trials. This review focuses on the results of the archetypal example of checkpoint blockade, anti-CTLA-4, in preclinical tumor models and clinical trials, while also highlighting other possible targets for immunological checkpoint blockade. © 2006 Elsevier Inc. All rights reserved. |
| Keywords: | unclassified drug; clinical trial; review; hepatitis; diarrhea; monotherapy; antineoplastic agent; neoplasms; t lymphocyte; animals; dacarbazine; glycoprotein gp 100; interleukin 2; ipilimumab; cancer immunotherapy; melanoma; immune system; dendritic cell; immunoglobulin; antineoplastic activity; kidney carcinoma; pruritus; rash; drug fatality; regulatory t lymphocyte; antigens, neoplasm; cancer vaccines; cpg island; epitope; colitis; enteritis; immunological adjuvant; tumor model; antigens, cd; cytotoxic t lymphocyte antigen 4; tumor vaccine; antibody; immunosuppressive agents; cd28 antigen; uveitis; antibodies, blocking; hypophysitis; ctla4 antibody |
| Journal Title: | Advances in Immunology |
| Volume: | 90 |
| ISSN: | 0065-2776 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2006-01-01 |
| Start Page: | 297 |
| End Page: | 339 |
| Language: | English |
| DOI: | 10.1016/s0065-2776(06)90008-x |
| PUBMED: | 16730267 |
| PROVIDER: | scopus |
| PMCID: | PMC1951510 |
| DOI/URL: | |
| Notes: | --- Chapter in "Cancer Immunotherapy" (ISBN: 978-0-12-022489-0) - "Cited By (since 1996): 124" - "Export Date: 4 June 2012" - "CODEN: ADIMA" - "Source: Scopus" |
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